TY - JOUR
T1 - Identification of critical residues for heterodimerization within the ligand-binding domain of retinoid X receptor
AU - Lee, S. K.
AU - Na, S. Y.
AU - Kim, H. J.
AU - Soh, J.
AU - Choi, H. S.
AU - Jae Woon Lee, Woon Lee
PY - 1998
Y1 - 1998
N2 - Nuclear receptors regulate transcription by binding to specific DNA response elements as homodimers or heterodimers with the retinoid X receptors (RXRs). The identity box (I-box), a 40- amino acid region within the ligand-binding domains of RXRs and other nuclear receptors, was recently shown to determine identity in the heterodimeric interactions. Here, we dissected this region in the yeast two-hybrid system by analyzing a series of chimeric receptors between human RXRα and rat hepatocyte nuclear factor 4 (HNF4), a distinct member of the nuclear receptor superfamily that prefers homodimerization. We found that the C-terminal 11-amino acid region of the RXR I-box was sufficient to direct chimeric receptors based on the HNF4 ligand-binding domain to heterodimerize with retinoic acid receptors or thyroid hormone receptors. Furthermore, we identified the hRXRα amino acids A416 and R421 of the 11-amino acid subregion as most critical determinants of heterodimeric interactions; i.e. mutant HNF4s incorporating only the hRXRα A416 or R421 heterodimerized with retinoic acid receptor.
AB - Nuclear receptors regulate transcription by binding to specific DNA response elements as homodimers or heterodimers with the retinoid X receptors (RXRs). The identity box (I-box), a 40- amino acid region within the ligand-binding domains of RXRs and other nuclear receptors, was recently shown to determine identity in the heterodimeric interactions. Here, we dissected this region in the yeast two-hybrid system by analyzing a series of chimeric receptors between human RXRα and rat hepatocyte nuclear factor 4 (HNF4), a distinct member of the nuclear receptor superfamily that prefers homodimerization. We found that the C-terminal 11-amino acid region of the RXR I-box was sufficient to direct chimeric receptors based on the HNF4 ligand-binding domain to heterodimerize with retinoic acid receptors or thyroid hormone receptors. Furthermore, we identified the hRXRα amino acids A416 and R421 of the 11-amino acid subregion as most critical determinants of heterodimeric interactions; i.e. mutant HNF4s incorporating only the hRXRα A416 or R421 heterodimerized with retinoic acid receptor.
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U2 - 10.1210/mend.12.3.0072
DO - 10.1210/mend.12.3.0072
M3 - Article
C2 - 9514150
AN - SCOPUS:0032230311
SN - 0888-8809
VL - 12
SP - 325
EP - 332
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 3
ER -